POS0912 THE EFFECT OF A 24-WEEK TRAINING ON METABOLIC PARAMETERS OF SKELETAL MUSCLE CELLS DERIVED FROM PATIENTS WITH ESTABLISHED IDIOPATHIC INFLAMMATORY MYOPATHIES.
Authors: M. Vokurková, L. Vernerová, S. Oreska, M. Špiritović, M. Klein, Z. Verner, M. Nemec, J. Ukropec, B. Ukropcová, M. Tomčík, J. Vencovský
Journal: Annals of the Rheumatic Diseases (2022)

Background Persistent muscle weakness after reduction of inflammation and resistance to immunosuppressive therapy in some patients with idiopathic inflammatory myopathies (IIM) suggest that not only immune but also non-immune mechanisms, such as mitochondrial abnormalities and metabolic disturbance, contribute to the pathogenesis of myositis. Exercise improves muscle function in IIM patients. Objectives To evaluate the effect of activities-of-daily-living, resistance and stability training on metabolic parameters of primary tissue culture myotubes established from muscle biopsies obtained from patients with established IIM. Methods Seven patients with established IIM underwent a 24-week supervised training focused on activities of daily living, muscle-strengthening and stability. Muscle biopsy was performed before and after the 24-week program in patients, and in healthy controls (n=9). Isolated skeletal muscle cells were grown and differentiated into myotubes for 6 days. After differentiation, the myotubes were cultured for another 24 hours in fresh medium, and then the conditioned media were collected, and the cells were harvested in TRIzol. A relative number of mitochondria was quantified by the ratio between mitochondrial gene (NADH dehydrogenase subunit 1) and reference nuclear gene (lipoprotein lipase) and determined by qPCR. Glucose, pyruvate, lactate, citrate, and fumarate were assessed in a conditioned medium using the comprehensive two-dimensional gas chromatography coupled to time of flight mass spectrometer. Results Patients significantly improved their muscle strength and endurance during the 24-week training [1]. There was no difference in the relative number of mitochondria in muscle tissue and myotubes between IIM patients and controls. A significant increase in the number of muscle tissue mitochondria was found in IIM patients after 24 weeks of training (p = 0.004), on average twofold. A similar effect was observed in cultured myotubes, with at least 4 of 7 IIM patients showing a twofold increase in mitochondria number. Compared with myotubes from HC, myotubes derived from IIM patients consumed non-significantly more glucose and pyruvate from the culture medium; however, their glucose and pyruvate utilization were significantly reduced as a result of the 24-week training (p = 0.016 and p = 0.030, respectively). Skeletal muscle cells from IIM patients before training intervention did not differ from HC cells in the amount of released lactate; however, the lactate concentration in the conditioned medium from myotubes obtained from patients after the 24-week training was significantly lower (p = 0.016). When measuring citrate cycle products released into the culture medium, no difference in citrate and fumarate secretion was observed between myotubes of myositis patients and myotubes of healthy controls. In contrast, their release was significantly (p &lt; 0.05) lower in myotubes from IIM patients after 24 weeks of training compared to muscle cells isolated prior to intervention. Conclusion In conclusion, 24 weeks of rehabilitation training in patients with IIM significantly increases the number of mitochondria in muscle tissue. Lower release of lactate and citrate cycle intermediates (citrate and fumarate) by myotubes obtained from patients after training intervention indicates an increase in mitochondrial functional capacity and confirms a positive response to exercise in muscles previously affected by the inflammatory process in IIM. References [1]Špiritović M, et al. Arthritis Res Ther. 2021;23(1):173. Acknowledgements This work was supported by the Ministry of Health of the Czech Republic grants nr. NU21-05-00322. Disclosure of Interests None declared